Preconditioning and Arrhythmias

Abstract

A brief episode of myocardial ischemia confers endogenous cardioprotection during a subsequent prolonged period of ischemia. This phenomenon, known as preconditioning, 1 offers one of the most powerful mechanisms for reducing the speed and extent of myocardial cell damage resulting from an acute or sustained ischemic insult. This protection has been shown to occur in a wide variety of animal species, including man, and exists in two forms, namely an early or classic preconditioning 1 and delayed or second window of protection. 2 The "gold standard" used in these animal studies for assessing a preconditioning effect has been measurement of the extent of limitation of infarct size. 3 Studies in humans therefore necessarily rely on a less direct approach. 4 For example, clinical observation has shown that the occurrence of episodes of angina shortly before a myocardial infarction reduces mortality and morbidity. 4,5 In the setting of percutaneous transluminal coronary angiography, it has been shown that measures of ischemia, such as angina and ST elevation, in the ECG occurring during the period when the coronary artery is occluded by the inflated balloon are less during a second balloon inflation compared with the first. 6 -8 These studies are not always easy to interpret, however, because of confounding variables such as uncertainties about the recruitment of collaterals in response to the preconditioning ischemia, the adequacy of the very short See p 3091duration of ischemia sometimes used during the preconditioning phase, and the use of the amount of ST segment shift in the ECG as a quantitative measure of ischemia. 4 One study largely overcomes the uncertainties with regard to collateral flow in patients undergoing percutaneous transluminal coronary angiography and demonstrates an antiarrhythmic effect of preconditioning. 9 Possibly the most direct evidence for the occurrence of preconditioning in humans comes from studies in patients undergoing coronary artery surgery, where it has been shown that the introduction of two 3-minute periods of global ischemia early in the operation reduced the loss of high energy phosphates 10 and troponin T after the subsequent prolonged period of ischemia during the fashioning of the coronary graft anastomoses. 11,12 Thus, overall, the available evidence supports the notion that preconditioning not only occurs in humans but does so within context of clinical procedures and as such may be of potential benefit to patients.Whereas preconditioning has been shown to dramatically reduce infarct size in all species studied, the situation with regard to surrogate endpoints 13 such as ventricular arrhythmias is less clear. The majority of studies in animal models report a reduction in arrhythmias after preconditioning protocols. 14,15 Some studies, on the other hand, report a worsening of arrhythmias. For example, in the original study by Murray et al, 1 there was a trend to an increased susceptibility to ventricular fibrillation (VF) in preconditioned dogs. In another study, although ...

Release of choline in the isolated heart, an indicator of ischemic phospholipid degradation and its protection by ischemic preconditioning: No evidence for a role of phospholipase D

“…IPC reduced the incidence of arrhythmias during reperfusion from 80% to 31%, an observation that is known since almost two decades (Shiki and Hearse, 1987;Taggert and Yellon, 2002).…”

Remote Ischemic Conditioning: Evolution of the Concept, Mechanisms, and Clinical Application

“…The studies to date examining the second window effect have been in animal models of local ischemia 3 . The IPC also alleviates myocardial dysfunction‐associated ventricular arrhythmias 4‐6 . The duration and timing of the preconditioning stimulus appear to influence the degree of protection 7‐10 .…”

Cardiac Preconditioning during Percutaneous Coronary Interventions

“…Although the effects of ischemic PC on arrhythmias are unresolved [23], ischemic PC appears to possess important anti-arrhythmic actions during revascularization: Salubrious benefits on ventricular ectopy [24] and QT dispersion [25] during PCI, and on the incidence of ventricular fibrillation/tachycardia during surgical revascularization [26] have been well documented.…”